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MiR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma.

ABSTRACT: miR-31 is oncogenic for head and neck squamous cell carcinoma (HNSCC). Proteins containing the AT-rich interacting domain (ARID) modulate the accessibility of chromatin to the transcription machinery needed for gene expression. In this study, we showed that miR-31 was able to target ARID1A in HNSCC. HNSCC tumors had an inverse miR-31 and ARID1A expression. miR-31 associated oncogenicities were rescued by ARID1A expression in HNSCC cells. Furthermore, ARID1A repressed the stemness properties and transcriptional activity of Nanog/OCT4/Sox2/EpCAM via the protein's affinity for AT-rich sites within promoters. HNSCC patients with tumors having high level of miR-31 expression and high levels of Nanog/OCT4/Sox2/EpCAM expression, together with low level of ARID1A expression, were found to have the worst survival. This study provides novel mechanistic clues demonstrating that miR-31 inhibits ARID1A and that this enriches the oncogenicity and stemness of HNSCC.

SUBMITTER: Lu WC

PROVIDER: S-EPMC5302987 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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miR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma.

Lu Wen-Cheng WC Liu Chung-Ji CJ Tu Hsi-Feng HF Chung Yu-Tung YT Yang Cheng-Chieh CC Kao Shou-Yen SY Chang Kuo-Wei KW Lin Shu-Chun SC

Oncotarget 20160801 35

miR-31 is oncogenic for head and neck squamous cell carcinoma (HNSCC). Proteins containing the AT-rich interacting domain (ARID) modulate the accessibility of chromatin to the transcription machinery needed for gene expression. In this study, we showed that miR-31 was able to target ARID1A in HNSCC. HNSCC tumors had an inverse miR-31 and ARID1A expression. miR-31 associated oncogenicities were rescued by ARID1A expression in HNSCC cells. Furthermore, ARID1A repressed the stemness properties and ...[more]

PMID: 27528032

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Project description:Patients who have undergone curative?intent therapy for head and neck squamous cell carcinoma (HNSCC) exhibit a high rate of development of second primary tumors (SPTs), which are frequently lethal. A chemoprevention strategy that prevents SPTs would have a major impact on patient outcomes. Sulforaphane, a naturally?occurring compound derived from cruciferous vegetables exhibits chemopreventive activity against HNSCC in a preclinical model. The effects of sulforaphane are considered to be mediated, in large part, through increased protein expression of the transcription factor nuclear factor erythroid 2?related factor 2 (NRF2). Development of sulforaphane chemoprevention for HNSCC would benefit from the identification of robust biomarkers of sulforaphane activity in HNSCC cells and normal mucosal epithelial cells. The present study revealed that sulforaphane potently induces multiple oxidative stress?associated genes at the RNA and protein levels, in HNSCC cells and Het?1A cells, a non?tumorigenic mucosal epithelial cell line. In the present analysis, HMOX1 and HSPA1A were identified as the most highly upregulated genes following sulforaphane treatment, suggesting their potential value as biomarkers to guide clinical trials. Sulforaphane induction of HMOX1 and HSPA1A was validated in vivo in murine tissues. Furthermore, the impact of sulforaphane treatment of HNSCC cells on the expression levels of natural killer group 2D (NKG2D) and DNAX accessory molecule?1 (DNAM?1) ligands, which are activators of natural killer (NK) cells, was examined. NRF2?dependent upregulation of the NKG2D ligand MICA/B was observed. However, only one of the six HNSCC cell lines studied exhibited enhanced sensitivity to NK cell?mediated killing following sulforaphane treatment, suggesting that this may not be a general mechanism of sulforaphane chemopreventive activity in HNSCC. In summary, the present study identified robust biomarkers of sulforaphane activity in HNSCC and normal tissues, supporting their application in the development of sulforaphane chemoprevention approaches for HNSCC.

Dataset Information

MiR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma.

Publications

miR-31 targets ARID1A and enhances the oncogenicity and stemness of head and neck squamous cell carcinoma.

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